Controlled release formulations of pharmaceutical agents is an extremely large market in the pharmaceutical and medical fields. A number of types of controlled release dosage forms are known, including matrix tablet systems incorporating active ingredients, fillers and various types of excipients. The very different properties of numerous different types of pharmaceutically active ingredients has necessitated the development of a number of different drug delivery systems utilizing polymer technology in order to provide an appropriate release of a particular medicament after oral ingestion by a patient.
U.S. Pat. Nos. 4,601,894 and 4,687,757 describe a controlled release drug delivery system which contains hydroxypropyl cellulose (HPMC) and a second polymer such as ethylcellulose, methylcellulose, sodium carboxymethyl cellulose or other cellulose ethers. U.S. Pat. No. 4,680,323 describes a carrier system comprising hydroxypropyl cellulose and a carboxy vinyl polymer. U.S. Pat. No. 4,695,591 describes the use of HPMC for mediating controlled release of pharmaceutically active substances. U.S. Pat. No. 4,994,276 teaches a free-flowing directly compressible granulation useful as a slow release pharmaceutical excipient. The excipient includes a hydrophilic matrix which includes a heteropolysaccharide and a polysaccharide material capable of cross-linking the heteropolysaccharide.
U.S. Pat. No. 4,167,558 teaches a novel sustained release tableted formulation for oral administration. The formulation is hydrodynamically balanced to be buoyant in gastric juice thereby remaining in the stomach for an extended period of time. U.S. Pat. No. 4,259,314 teaches a method and composition for the preparation of controlled long-acting pharmaceuticals using a dry carrier or base material comprising an effective amount of hydroxypropyl methylcellulose and hydroxypropyl cellulose suitable for use with both hygroscopic and non-hygroscopic materials. The controlled long-acting products of the invention are suitable for use in the form of lozenges, bucal tablets, oral tablets or suppositories.
U.S. Pat. No. 4,308,251 teaches a tablet formulation comprising an effective amount of an active acidic therapeutic agent, a release-controlling agent and an erosion-promoting agent in relative amounts to provide a criticality factor of less than 450, and in proportions of release-controlling and erosion-promoting agent, respectively, between 0.8-1.6 and 1.0-7.5 weight percent per tablet. The tablets of this invention exhibit zero order release in vitro and closely approximate zero order absorption in vivo.
U.S. Pat. No. 4,361,545 teaches a class of solid pharmaceutical formulations which provides slow, zero order in vivo release of a wide range of pharmaceutically active ingredients upon oral administration. A broad range of release rates can be preselected by suitable adjustments of tablet properties. The formulations are based upon control of active ingredient release from the surface of the tablet via a controlled surface erosion mechanism.
U.S. Pat. No. 4,389,393 teaches a carrier base material combined with a therapeutically active medicament and shaped and compressed to a solid unit dosage form having a regular and prolonged release pattern upon administration, the carrier base material being one or more hydroxypropylmethylcelluloses or a mixture of one or more hydroxypropylmethylcelluloses having a methoxy content of 16-24 weight %, a hydroxypropoxyl content of 4-32 weight % and an average molecular weight of at least 50,000.
U.S. Pat. No. 4,525,345 teaches a constant release rate indomethacin formulation in tablet unit dosage form containing an admixture of from 50 to 200 mg of indomethacin, from about 1.7 to 3.7 weight percent of a slow-dissolving, water-insoluble cellulose derivative, from about 1.5 to 5.0 weight percent of a tableting disintegrant, and from about 40 to 80 weight percent of a pharmaceutically acceptable bulking agent or diluent.
U.S. Pat. No. 4,556,678 teaches a tablet consisting essentially of a therapeutically effective amount of propranolol to provide a sustained release thereof over a prolonged period of time. The tablet comprises compressed granules having from about 0.1 to about 10 parts by weight hydroxypropyl methylcellulose and about one part by weight hydroxpropyl cellulose.
U.S. Pat. No. 4,692,337 teaches a sustained release pharmaceutical tablet comprising theophylline and ethyl cellulose uniformly dispersed therein in an amount of 5 to 200 parts by weight of ethyl cellulose based on 100 parts by weight of the theophylline.
U.S. Pat. No. 4,756,911 teaches a controlled release pharmaceutical formulation in the form of a coated tablet, containing a core portion from which medicament, such as procainamide hydrochloride, is slowly released over a controlled length of time. The core also includes one or more primary hydrocolloid gelling agents which is a hydropropymethyl cellulose having a viscosity of within the range of from about 1,000 to about 6,000 centipoises in 2% solution at 20° C., a methoxyl content of 28-30% and optionally a secondary hydrocarbon gelling agent, such as hydroxpropyl cellulose and/or methyl cellulose.
U.S. Pat. No. 5,073,380 teaches a pharmaceutical sustained release tablet containing a pharmaceutical active, hydroxyethyl cellulose, a wicking agent, povidone, pregelatinized starch, lubricant and a glidant.
U.S. Pat. No. 5,417,982 teaches a controlled release formulation for use with a variety of drugs or hormones in microspherical form. The drug or hormone, e.g. bovine somatropine, is suspended in a polymer matrix formed from at least two highly water soluble biodegradable polymers. The microspheres are coated with a (δ, 1 lactide-glycolide) copolymer.
U.S. Pat. No. 4,968,509 teaches an acetaminophen-sustained release tablet formed by making a wet granulation, using Povidone (PVP) in water or alcohol-water as the granulating fluid which is mixed with acetaminophen, hydroxyethyl cellulose, a wicking agent e.g. microcrystalline cellulose, then drying and milling the granulation and blending with dry powdered erosion promoter, e.g. pregelatinized starch, wicking agent, lubricant e.g. magnesium stearate and glidant e.g. silicon dioxide, and compressing the resultant granulation.
U.S. Pat. No. 5,462,747 teaches a pharmaceutical sustained release homogeneous tablet formed by making a wet granulation using povidone (PVP) in alcohol as the granulating fluid mixed with a pharmaceutical active, ethylcellulose, a wicking agent, e.g. microcrystalline cellulose, an erosion promoter, e.g. pregelatinized starch, then drying and milling the granulation and blending with a dry powdered erosion promotor, wicking agent, lubricant and glidant.
U.S. Pat. No. 5,543,154 teaches a device for the controlled delivery of a beneficial agent as a gelatinous dispersion consisting of a core which contains a beneficial agent, a polymer which forms gelatinius micoroscopic particles upon hydration and if desired an agent to modulate the hydration of the polymer; and an impermeable, insoluble coating which adheres to and surrounds the core and contains apertures which provides an area for the hydration and release of a disperson comprising gelatinous microscropic particles.
U.S. Pat. No. 5,439,687 teaches pharmaceutical dosage forms for the daily oral administration of nifedipine or of another calcium antagonist of the dihydrophyridine type, characterised by the homogeneous matrix containing 2-50% by weight of hydroxypropylmethylcellulose having an average molecular weight of 20,000-250,000, 5-60% by weight of a calcium antagonist of the dihydropyridine type, as well as excipients compatible with the formulation.
U.S. Pat. No. 5,264,446 teaches a solid pharmaceutical composition of nifedipine crystals having specific surface area of 1-4 m2/g in the form of tablets, pills, drages, capsules, suppositories, sachets or two layer tablets resulting in sustained release.
While these systems can provide for sustained release of a selected active ingredient, most of these systems have the disadvantage of being affected by the presence of food and gastrointestinal engines in the gastrointestinal (GI) tract. Therefore, the active ingredient is often not delivered consistent and reproducible manner. In addition, osmotic and press coated tablets are particularly difficult and expensive to manufacture.
It is therefore particularly desirable to design an efficient drug delivery system that is capable of controlled drug delivery of both high dose, highly soluble, hydrophillic and low dose, poorly soluble, hydrophobic pharmaceutically active substance(s) into the gastrointestinal tract (GIT) in order to provide sustained therapeutic effects for over 24 hours with only a single dose and without any food effect. It is also highly desirable to develop a drug delivery system that is relatively easy and inexpensive to manufacture and more efficient in providing a sustained release of pharmaceutical agents than the known controlled delivery systems.